Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted ...Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.Conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.展开更多
Despite enormous efforts to achieve the goal of eliminating mother-to-child transmission of HIV-1, it remains a major challenge for many countries in sub-Saharan Africa, particularly Mali. Our objective is to assess c...Despite enormous efforts to achieve the goal of eliminating mother-to-child transmission of HIV-1, it remains a major challenge for many countries in sub-Saharan Africa, particularly Mali. Our objective is to assess changes in the rate of mother-to-child transmission of HIV-1. We conducted a cross-sectional study between January 1, 2009 to December 31, 2018 (10 years) of early diagnosis activity in newborns and children born to HIV-1-positive mothers at the National Institute for Public Health (INSP). The samples came from health and referral centers in mali. All samples were received at the Laboratory of Molecular Biology at the INSP. Proviral DNA extraction was performed from a blood spot sample with a Roche DNA kit, Cobas AmpliPrep/Cobas TaqMan HIV-1 qualitative Test, V2.0 (Roche Molecular System, Inc, USA) following the company procedures. Molecular diagnosis was performed using the same kits using an algorithm of three identical PCRs. The Epi Info version 7 software was used for data analysis with a significance threshold of 5%. A total of 10,714 samples of infants and children born to HIV-positive mothers were analyzed by PCR. Ninety-six percent of mothers were on ARV prophylaxis (AZT 3TC NVP and AZT NVP) and 60% of newborns received the same ARV prophylaxis. Of these children, 956 tested positive with an overall transmission rate of 8.92%, varying between 7.27% in 2009 and 08.01% in 2018. This rate was relatively low among children receiving prophylaxis at 2.04% and remained high for children who received breastfeeding at 5.62%. However, the transmission rate remains low for those who have benefited from mixed and artificial breastfeeding at 1.58% and 1.27% respectively. A significant proportion of children remained infected by their mothers during pregnancy, childbirth or breastfeeding. This study shows the importance of early diagnosis of HIV in children using molecular technology.展开更多
The emergence of antiretroviral resistance mutations represents a major threat to the achievement of national and global goals for the elimination of HIV-1 infection. The global strategy in 2019 in Cte d'Ivoire is...The emergence of antiretroviral resistance mutations represents a major threat to the achievement of national and global goals for the elimination of HIV-1 infection. The global strategy in 2019 in Cte d'Ivoire is a new national policy for the management of people living with HIV with the administration of dolutegravir (DTG)-based fixed-dose combination. The aim of our study was to evaluate HIV-1 resistance to antiretrovirals (ARVs) in infected adult subjects in Cte d’Ivoire in the context of a systematic switch to a DTG-based combination. Between February 2022 and October 2023, a cross-sectional survey with random sampling was conducted in 06 services caring for people living with HIV. A total of 139 participants were included in the study. Adults with a viral load ≥ 1000 copies/mL were tested for HIV-1 ARV resistance mutations. Molecular analyses were performed using protocol of ANRS-MIE (National Agency for Research on AIDS and emerging infectious diseases). The interpretation is performed by HIVGRAD (https://www.hiv-grade.de/cms/grade/). The frequencies of HIV-1 resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), integrase inhibitors (IINTs) and protease inhibitors (PIs) were 82%, 73%, 19% and 11% respectively. The main mutations observed in the different classes were K103N (45%), M184V (64%), E157Q (19%) and L10V/M46I/A71V/I54V (6%) respectively. This study reveals the emergence of resistance to DTG-based fixed-dose combinations, favored by high rates of resistance to NRTIs and NNRTIs. This finding underlines the need for enhanced viral load monitoring and HIV-1 genotyping tests to guide the choice of NRTIs for combination therapy. In addition, monitoring for mutations to second-generation NRTIs is essential, given the scale-up of DTG-based regimens currently underway in Cte d’Ivoire.展开更多
Introduction: HIV, the human immunodeficiency virus, is the etiological agent of acquired immunodeficiency syndrome (AIDS). The aim of this study was to assess the evolution of the viral load in patients under treatme...Introduction: HIV, the human immunodeficiency virus, is the etiological agent of acquired immunodeficiency syndrome (AIDS). The aim of this study was to assess the evolution of the viral load in patients under treatment. Methodology: This was a study carried out from July 2017 to June 2022 at the Point G University Hospital laboratory. The determination of the viral load of patients was carried out by PCR on the ABOTT M2000sp/rt platform. Results: A total of 129 patients infected with HIV-1, aged 19 to 72 years with a mean age of 40.05 years ± 10.71;all on antiretroviral chemotherapy. The female gender predominated among our patients. The most common treatment regimen was 2INTI + 1INNTI with 72.9% followed by 2INTI + 1INI with 13.2%. As for the combinations of molecules, the combination TDF + 3TC + EFV and TDF + 3TC + DTG predominated, respectively 65.1% and 13.2%. 89.9% of our patients had undetectable viremia after 12 months of treatment (p < 0.005) with an average viral load which had evolved from 681315.65 copies/ml ± 1616908.484 to M0 at 5742.36 copies /ml ± 35756.883 at M12 (p Conclusion: Generally speaking, antiretroviral treatment had contributed to controlling viral loads, however the therapeutic combination TDF + 3TC + DTG had made it possible to obtain more patients with undetectable viremia instead.展开更多
目的对保定市新发现的1株pol区不能明确分型的HIV-1毒株(BD226AJ)进行近似全长基因组扩增,并分析其亚型、重组模式和基因特点。方法提取患者血浆中HIV-1RNA并逆转录为cDNA,使用近末端稀释法分2段对其进行近似全长基因组扩增并测序。使用...目的对保定市新发现的1株pol区不能明确分型的HIV-1毒株(BD226AJ)进行近似全长基因组扩增,并分析其亚型、重组模式和基因特点。方法提取患者血浆中HIV-1RNA并逆转录为cDNA,使用近末端稀释法分2段对其进行近似全长基因组扩增并测序。使用jpHMM和SimPlot 3.5软件对近似全长基因组序列进行重组模式和重组断点分析,采用MEGA 6.0软件分片段构建Neighbor-joining系统进化树进一步确认重组断点的准确性。构建该近似全长基因组序列及各亚型片段Neighbor-joining系统进化树,分析该毒株的亲本来源。结果经过近似全长基因组扩增、测序、序列拼接后,获得1条长度为8830 bp的HIV-1近似全长基因组序列。重组分析结果显示,该序列是由CRF01_AE和B亚型重组形成的,其近似全长基因组序列被3个断点分成了4个亚型片段,分别为ICRF01_AE(HXB2,823—4224 nt)、Ⅱ_(B)(HXB2,4225—5991 nt)、ⅢCRF01_AE(HX B2,5992—9295 nt)、ⅣB(HXB2,9296—9406 nt)。各亚型基因片段的系统进化树分析进一步表明该序列的可能亲本来源为CRF01_AE和B亚型。HIV BLAST的结果显示,该序列与CRF112_01B的相似性为96%,系统进化树分析进一步验证该序列与北京市男男性行为者(men who have sex with men,MSM)中的CRF112_01B序列聚集。结论本研究在保定市MSM人群中发现了1例由CRF01_AE和B亚型重组的新型重组毒株CRF112_01B,提示HIV-1CRF112_01B已通过MSM人群传入河北,并开始在保定市传播,因此加强该亚型或者类似新型毒株的监测,对有关部门采取针对性防控措施和遏制新型重组毒株在本地区的传播和流行具有重要意义。展开更多
Objective：Menage a trois 1（MAT1）is a targeting subunit of cyclin-dependent kinase-activating kinase and general transcription factor IIH kinase,which modulates cell cycle,transcription and DNA repair.Its dysregulat...Objective：Menage a trois 1（MAT1）is a targeting subunit of cyclin-dependent kinase-activating kinase and general transcription factor IIH kinase,which modulates cell cycle,transcription and DNA repair.Its dysregulation is responsible for diseases including cancers.To further explore the role of MAT1 in breast cancer,we investigated the pathways in which MAT1 might be involved,the association between MAT1 and molecular subtypes,and the role of MAT1 in clinical outcomes of breast cancer patients.Methods：We conducted immunohistochemistry staining on tissue microarray and immunofluorescence staining on sections of MAT1 stable breast cancer cells.Also,we performed Kyoto Encyclopedia of Genes and Genomes pathway analysis,correlation analysis and prognosis analysis on public databases.Results：MAT1 was involved in multiple pathways including normal physiology signaling and disease-related signaling.Furthermore,MAT1 positively correlated with the protein status of estrogen receptor and progesterone receptor,and was enriched in luminal-type and human epidermal growth factor receptor 2-enriched breast cancer in comparison with basal-like subtype at both m RNA and protein levels.Correlation analysis revealed significant association between MAT1 m RNA amount and epithelial markers,mesenchymal markers,cancer stem cell markers,apoptosis markers,transcription markers and oncogenes.Consistently,the results of immunofluorescence stain indicated that MAT1 overexpression enhanced the protein abundance of epidermal growth factor receptor,vimentin,sex determining region Y-box 2 and sine oculis homeobox homolog 1.Importantly,Kaplan-Meier Plotter analysis reflected that MAT1 could serve as a prognostic biomarker predicting worse relapse-free survival and metastasis-free survival.Conclusions：MAT1 is correlated with molecular subtypes and is associated with unfavorable prognosis for breast cancer patients.展开更多
Objective The mode of human immunodeficiency virus(HIV) transmission via injection drug use(IDU)still exists, and the recent shift in IDU-related transmission of HIV infection is largely unknown. The purpose of this s...Objective The mode of human immunodeficiency virus(HIV) transmission via injection drug use(IDU)still exists, and the recent shift in IDU-related transmission of HIV infection is largely unknown. The purpose of this study was to analyze the spatiotemporal sources and dynamics of HIV-1 transmission through IDU in Guangxi.Methods We performed a molecular epidemiological investigation of infections across Guangxi from2009 to 2019. Phylogenetic and Bayesian time-geographic analyses of HIV-1 sequences were performed to confirm the characteristics of transmission between IDUs in combination with epidemiological data.Results Among the 535 subjects, CRF08_BC(57.4%), CRF01_AE(28.4%), and CRF07_BC(10.7%) were the top 3 HIV strains;72.6% of infections were linked to other provinces in the transmission network;93.6% of sequence-transmitted strains were locally endemic, with the rest coming from other provinces,predominantly Guangdong and Yunnan;92.1% of the HIV transmission among people who inject drugs tended to be transmitted between HIV-positive IDUs.Conclusion HIV recombinants were high diversity, and circulating local strains were the transmission sources among IDUs in Guangxi. However, there were still cases of IDUs linked to other provinces.Coverage of traditional prevention strategies should be expanded, and inter-provincial collaboration between Guangxi, Yunnan, and Guangdong provinces should be strengthened.展开更多
基金supported by grants from the 2021 Graduate Education Innovation Program Project of Guangxi Zhuang Autonomous Region [YCBZ2021041]the National innovative training program for college students [202100001580]grants from the National Natural Science Foundation of China [NSFC,31860040]。
文摘Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.Conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.
文摘Despite enormous efforts to achieve the goal of eliminating mother-to-child transmission of HIV-1, it remains a major challenge for many countries in sub-Saharan Africa, particularly Mali. Our objective is to assess changes in the rate of mother-to-child transmission of HIV-1. We conducted a cross-sectional study between January 1, 2009 to December 31, 2018 (10 years) of early diagnosis activity in newborns and children born to HIV-1-positive mothers at the National Institute for Public Health (INSP). The samples came from health and referral centers in mali. All samples were received at the Laboratory of Molecular Biology at the INSP. Proviral DNA extraction was performed from a blood spot sample with a Roche DNA kit, Cobas AmpliPrep/Cobas TaqMan HIV-1 qualitative Test, V2.0 (Roche Molecular System, Inc, USA) following the company procedures. Molecular diagnosis was performed using the same kits using an algorithm of three identical PCRs. The Epi Info version 7 software was used for data analysis with a significance threshold of 5%. A total of 10,714 samples of infants and children born to HIV-positive mothers were analyzed by PCR. Ninety-six percent of mothers were on ARV prophylaxis (AZT 3TC NVP and AZT NVP) and 60% of newborns received the same ARV prophylaxis. Of these children, 956 tested positive with an overall transmission rate of 8.92%, varying between 7.27% in 2009 and 08.01% in 2018. This rate was relatively low among children receiving prophylaxis at 2.04% and remained high for children who received breastfeeding at 5.62%. However, the transmission rate remains low for those who have benefited from mixed and artificial breastfeeding at 1.58% and 1.27% respectively. A significant proportion of children remained infected by their mothers during pregnancy, childbirth or breastfeeding. This study shows the importance of early diagnosis of HIV in children using molecular technology.
文摘The emergence of antiretroviral resistance mutations represents a major threat to the achievement of national and global goals for the elimination of HIV-1 infection. The global strategy in 2019 in Cte d'Ivoire is a new national policy for the management of people living with HIV with the administration of dolutegravir (DTG)-based fixed-dose combination. The aim of our study was to evaluate HIV-1 resistance to antiretrovirals (ARVs) in infected adult subjects in Cte d’Ivoire in the context of a systematic switch to a DTG-based combination. Between February 2022 and October 2023, a cross-sectional survey with random sampling was conducted in 06 services caring for people living with HIV. A total of 139 participants were included in the study. Adults with a viral load ≥ 1000 copies/mL were tested for HIV-1 ARV resistance mutations. Molecular analyses were performed using protocol of ANRS-MIE (National Agency for Research on AIDS and emerging infectious diseases). The interpretation is performed by HIVGRAD (https://www.hiv-grade.de/cms/grade/). The frequencies of HIV-1 resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), integrase inhibitors (IINTs) and protease inhibitors (PIs) were 82%, 73%, 19% and 11% respectively. The main mutations observed in the different classes were K103N (45%), M184V (64%), E157Q (19%) and L10V/M46I/A71V/I54V (6%) respectively. This study reveals the emergence of resistance to DTG-based fixed-dose combinations, favored by high rates of resistance to NRTIs and NNRTIs. This finding underlines the need for enhanced viral load monitoring and HIV-1 genotyping tests to guide the choice of NRTIs for combination therapy. In addition, monitoring for mutations to second-generation NRTIs is essential, given the scale-up of DTG-based regimens currently underway in Cte d’Ivoire.
文摘Introduction: HIV, the human immunodeficiency virus, is the etiological agent of acquired immunodeficiency syndrome (AIDS). The aim of this study was to assess the evolution of the viral load in patients under treatment. Methodology: This was a study carried out from July 2017 to June 2022 at the Point G University Hospital laboratory. The determination of the viral load of patients was carried out by PCR on the ABOTT M2000sp/rt platform. Results: A total of 129 patients infected with HIV-1, aged 19 to 72 years with a mean age of 40.05 years ± 10.71;all on antiretroviral chemotherapy. The female gender predominated among our patients. The most common treatment regimen was 2INTI + 1INNTI with 72.9% followed by 2INTI + 1INI with 13.2%. As for the combinations of molecules, the combination TDF + 3TC + EFV and TDF + 3TC + DTG predominated, respectively 65.1% and 13.2%. 89.9% of our patients had undetectable viremia after 12 months of treatment (p < 0.005) with an average viral load which had evolved from 681315.65 copies/ml ± 1616908.484 to M0 at 5742.36 copies /ml ± 35756.883 at M12 (p Conclusion: Generally speaking, antiretroviral treatment had contributed to controlling viral loads, however the therapeutic combination TDF + 3TC + DTG had made it possible to obtain more patients with undetectable viremia instead.
文摘目的对保定市新发现的1株pol区不能明确分型的HIV-1毒株(BD226AJ)进行近似全长基因组扩增,并分析其亚型、重组模式和基因特点。方法提取患者血浆中HIV-1RNA并逆转录为cDNA,使用近末端稀释法分2段对其进行近似全长基因组扩增并测序。使用jpHMM和SimPlot 3.5软件对近似全长基因组序列进行重组模式和重组断点分析,采用MEGA 6.0软件分片段构建Neighbor-joining系统进化树进一步确认重组断点的准确性。构建该近似全长基因组序列及各亚型片段Neighbor-joining系统进化树,分析该毒株的亲本来源。结果经过近似全长基因组扩增、测序、序列拼接后,获得1条长度为8830 bp的HIV-1近似全长基因组序列。重组分析结果显示,该序列是由CRF01_AE和B亚型重组形成的,其近似全长基因组序列被3个断点分成了4个亚型片段,分别为ICRF01_AE(HXB2,823—4224 nt)、Ⅱ_(B)(HXB2,4225—5991 nt)、ⅢCRF01_AE(HX B2,5992—9295 nt)、ⅣB(HXB2,9296—9406 nt)。各亚型基因片段的系统进化树分析进一步表明该序列的可能亲本来源为CRF01_AE和B亚型。HIV BLAST的结果显示,该序列与CRF112_01B的相似性为96%,系统进化树分析进一步验证该序列与北京市男男性行为者(men who have sex with men,MSM)中的CRF112_01B序列聚集。结论本研究在保定市MSM人群中发现了1例由CRF01_AE和B亚型重组的新型重组毒株CRF112_01B,提示HIV-1CRF112_01B已通过MSM人群传入河北,并开始在保定市传播,因此加强该亚型或者类似新型毒株的监测,对有关部门采取针对性防控措施和遏制新型重组毒株在本地区的传播和流行具有重要意义。
基金supported by the National Natural Science Foundation of China (Grant No.81572608 and 81172422)the Wuhan Science and Technology Bureau (Grant No.2017060201010170)
文摘Objective：Menage a trois 1（MAT1）is a targeting subunit of cyclin-dependent kinase-activating kinase and general transcription factor IIH kinase,which modulates cell cycle,transcription and DNA repair.Its dysregulation is responsible for diseases including cancers.To further explore the role of MAT1 in breast cancer,we investigated the pathways in which MAT1 might be involved,the association between MAT1 and molecular subtypes,and the role of MAT1 in clinical outcomes of breast cancer patients.Methods：We conducted immunohistochemistry staining on tissue microarray and immunofluorescence staining on sections of MAT1 stable breast cancer cells.Also,we performed Kyoto Encyclopedia of Genes and Genomes pathway analysis,correlation analysis and prognosis analysis on public databases.Results：MAT1 was involved in multiple pathways including normal physiology signaling and disease-related signaling.Furthermore,MAT1 positively correlated with the protein status of estrogen receptor and progesterone receptor,and was enriched in luminal-type and human epidermal growth factor receptor 2-enriched breast cancer in comparison with basal-like subtype at both m RNA and protein levels.Correlation analysis revealed significant association between MAT1 m RNA amount and epithelial markers,mesenchymal markers,cancer stem cell markers,apoptosis markers,transcription markers and oncogenes.Consistently,the results of immunofluorescence stain indicated that MAT1 overexpression enhanced the protein abundance of epidermal growth factor receptor,vimentin,sex determining region Y-box 2 and sine oculis homeobox homolog 1.Importantly,Kaplan-Meier Plotter analysis reflected that MAT1 could serve as a prognostic biomarker predicting worse relapse-free survival and metastasis-free survival.Conclusions：MAT1 is correlated with molecular subtypes and is associated with unfavorable prognosis for breast cancer patients.
基金National Natural Science Foundation of China [grant no. 82060610]National Natural Science Foundation of China [grant no. 82103899]+2 种基金Guangxi Scientific and Technological Key Project[Gui Ke AB19245038]Guangxi Scientific and Technological Key Project [Guike 2022AC23005, 2022AC20031,2022JJA141110]Science and Technology Project of Nanning [20223051]。
文摘Objective The mode of human immunodeficiency virus(HIV) transmission via injection drug use(IDU)still exists, and the recent shift in IDU-related transmission of HIV infection is largely unknown. The purpose of this study was to analyze the spatiotemporal sources and dynamics of HIV-1 transmission through IDU in Guangxi.Methods We performed a molecular epidemiological investigation of infections across Guangxi from2009 to 2019. Phylogenetic and Bayesian time-geographic analyses of HIV-1 sequences were performed to confirm the characteristics of transmission between IDUs in combination with epidemiological data.Results Among the 535 subjects, CRF08_BC(57.4%), CRF01_AE(28.4%), and CRF07_BC(10.7%) were the top 3 HIV strains;72.6% of infections were linked to other provinces in the transmission network;93.6% of sequence-transmitted strains were locally endemic, with the rest coming from other provinces,predominantly Guangdong and Yunnan;92.1% of the HIV transmission among people who inject drugs tended to be transmitted between HIV-positive IDUs.Conclusion HIV recombinants were high diversity, and circulating local strains were the transmission sources among IDUs in Guangxi. However, there were still cases of IDUs linked to other provinces.Coverage of traditional prevention strategies should be expanded, and inter-provincial collaboration between Guangxi, Yunnan, and Guangdong provinces should be strengthened.
